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Collagen is an abundant protein found in the extracellular matrix of many tissues. Due to its biocompatibility, it is a potentially ideal biomaterial for many tissue engineering applications. However, harvested collagen often requires restructuring into a three-dimensional matrix to facilitate applications such as implantation into poorly accessible tissue cavities. The aim of the current study was to produce a conformable collagen-based scaffold material capable of supporting tissue regeneration for use in wound repair applications. Microporous collagen spheres were prepared using a thermally induced phase separation (TIPS) technique and their biocompatibility was assessed. The collagen spheres were successfully cross-linked with glutaraldehyde vapour, rendering them mechanically more stable. When cultured with myofibroblasts the collagen spheres stimulated a prolonged significant increase in secretion of the angiogenic growth factor, vascular endothelial growth factor (VEGF), compared with cells alone. Control polycaprolactone (PCL) spheres failed to stimulate a similar prolonged increase in VEGF secretion. An enhanced angiogenic effect was also seen in vivo using the chick embryo chorioallantoic membrane assay, where a significant increase in the number of blood vessels converging towards collagen spheres was observed compared with control PCL spheres. The results from this study indicate that microporous collagen spheres produced using TIPS are biologically active and could offer a novel conformable scaffold for tissue regeneration in poorly accessible wounds.

Conformable scaffold materials capable of rapid vascularization and tissue infiltration would be of value in the therapy of inaccessible wounds. Microporous spheres of poly(D,L-lactide-co-glycolide) (PLGA) containing bioactive glass (BG) were prepared using a thermally induced phase separation (TIPS) technique, and the bioactivity, in vitro degradation, and tissue integration of the microporous spheres were assessed. Microporous spheres containing 10% (w/w) BG stimulated a significant increase in vascular endothelial growth factor secretion from myofibroblasts consistently over a 10-day period (p < 0.01) compared with the neat PLGA microporous spheres. The microporous spheres degraded steadily in vitro over a 16-week period, with the neat PLGA microporous spheres retaining 82% of their original weight and microporous spheres containing 10% (w/w) BG retaining 77%. Both types of microporous spheres followed a similar pattern of size reduction throughout the degradation study, resulting in a 23% and 20% reduction after 16 weeks for the neat PLGA microporous spheres and PLGA microporous spheres containing 10% (w/w) BG, respectively (p < 0.01). After in vivo implantation into a subcutaneous wound model, the TIPS microporous spheres became rapidly integrated (interspherically and intraspherically) with host tissue, including vascularization of voids inside the microporous sphere. The unique properties of TIPS microporous spheres make them ideally suited for regenerative medicine applications where tissue augmentation is required.

Attempts to stimulate therapeutic angiogenesis using gene therapy or delivery of recombinant growth factors, such as vascular endothelial growth factor (VEGF), have failed to demonstrate unequivocal efficacy in human trials. Bioactive glass stimulates fibroblasts to secrete significantly increased amounts of angiogenic growth factors and therefore has a number of potential applications in therapeutic angiogenesis. The aim of this study was to assess whether it is possible to encapsulate specific quantities of bioactive glass and fibroblasts into alginate beads, which will secrete growth factors capable of stimulating angiogenesis. Human fibroblasts (CCD-18Co) were encapsulated in alginate beads with specific quantities of 45S5 bioactive glass and incubated in culture medium (0-17 days). The conditioned medium was collected and assayed for VEGF or used to assess its ability to stimulate angiogenesis by measuring the proliferation of human dermal microvascular endothelial cells. At 17 days the beads were lysed and the amount of VEGF retained by the beads measured. Fibroblasts encapsulated in alginate beads containing 0.01% and 0.1% (w/v) 45S5 bioactive glass particles secreted increased quantities of VEGF compared with cells encapsulated with 0% or 1% (w/v) 45S5 bioactive glass particles. Lysed alginate beads containing 0.01% and 0.1% (w/v) 45S5 bioactive glass contained significantly more VEGF (p

Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of high-fat ethanol-containing food. Delivery of recombinant adiponectin into these mice dramatically alleviated hepatomegaly and steatosis (fatty liver) and also significantly attenuated inflammation and the elevated levels of serum alanine aminotransferase. These therapeutic effects resulted partly from the ability of adiponectin to increase carnitine palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while it decreased the activities of two key enzymes involved in fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase. Furthermore, adiponectin treatment could suppress the hepatic production of TNF-α and plasma concentrations of this proinflammatory cytokine. Adiponectin was also effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice. These results demonstrate a novel mechanism of adiponectin action and suggest a potential clinical application of adiponectin and its agonists in the treatment of liver diseases., published_or_final_version

affecting sphincter integrity and continence. Traditional surgical and medical approaches are not without their limitations and may result in either comorbidity, such as fecal incontinence, or incomplete healing of the fistulae. Over the last 2 decades these limitations have led to a paradigm shift toward the use of biomaterials, and more recently cell-based therapies, which have met with variable degrees of success. This review discusses the traditional and current methods of treatment, as well as emerging and possible alternative approaches that may improve fistula healing.